OP0158 COHORT ENRICHMENT STRATEGIES FOR PROGRESSIVE INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS FROM EUSTAR
Authors: A. M. Hoffmann-Vold, C. Brunborg, P. Airò, L. P. Ananyeva, L. Czirják, S. Guiducci, E. Hachulla, M. Li, C. Mihai, G. Riemekasten, P. Sfikakis, G. Valentini, O. Kowal-Bielecka, Y. Allanore, O. Distler
Journal: Annals of the Rheumatic Diseases (2022)

Background Enrichment strategies from clinical trials for progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) have been partly successful but have not been tested in a real life cohort. Objectives Analyse the efficacy, representativeness and feasibility of enrichment strategies in SSc-ILD patients from the EUSTAR cohort. Methods We applied the inclusion criteria of major recent SSc-ILD trials (focuSSced, SLS II and SENSCIS) in SSc-ILD patients and assessed progressive ILD, defined as absolute change in forced vital capacity (FVC) and as significant progression (FVC decline &gt;10%) over time. Data were compared to all patients and patients not fulfilling any inclusion criteria. Results In total, 2258 SSc-ILD patients were included, with 31.2% meeting SENSCIS, 5.8% SLS II, 1.6% focuSSced criteria and 1529 (67.7%) not meeting any criteria (Table 1). In the first 12+/-3 months, a slow FVC% decline of –0.1% was seen in the total, unselected cohort and in patients fulfilling SENSCIS criteria. Patients fulfilling criteria from focuSSced showed a strong FVC decline of –3.7%. Notably, patients enriched for SLS II criteria showed FVC improvement of +2.3% (Figure 1). Similarly, compared to the total unselected cohort, the number of significant progressive events was numerically higher in patients fulfilling focuSSced criteria, the same for SENSCIS criteria and even slightly lower for patients fulfilling the SLS2 criteria. Table 1. Demographics and baseline clinical characteristics of EUSTAR patients Not fulfilling any criteria (n=1529 ) focuSSced (n=36 ) SLS II (n=132 ) SENSCIS (n=704 ) Age, years (SD ) 58.4 (2.9) 51.5 (12.2) † 51.2 (12.7) † 54.2 (13.8) † Male, n (% ) 231 (15.1) 7 (19) 35 (27)** 156 (21)* Disease duration, months (SD ) 156.3 (99.4) 16.1 (13.9) † 40.7 (25.2) † 39.4 (23.9) † DcSSc, n (% ) 597 (43.8) 36 (100) † 85 (65) † 35 (52) † ATA, n (% ) 735 (51.1) 24 (67)* 85 (69) † 370 (56) mRSS, mean (SD ) 9.5 (8.3) 21 (6.5)* 13 (9.6)* 11 (9.2) GERD, n (% ) 1002 (65.9) 25 (69) 92 (70) 430 (62) ESR, mean (SD ) 27 (20.5) 43.1 (23) † 29.6 (19.6) † 24.7 (20.7) MMF, n (% ) 75 (16.5) 0 (0) † 0 (0) † 52 (22) † MTX, n (% ) 42 (9.2) 0 (0) † 2 (5) 20 (9) FVC % predicted, mean (SD ) 85.7 (22.5) 88 (13.6)* 66 (9.1) † 88 (19.8) DL CO % predicted, mean (SD ) 58.9 (21.5) 61 (12.7) 49(14.6) † 59 (14.2) NYHA class, n (% ) 3 261 (17.8) 6 (19) 28 (21) 72 (10)* 4 40 (2.7) 0 (0) 3 (2) 4 (1)* *P-value: 0.001–0.05; † P&lt;0.001, between focuSSced, SENSCIS or SLS compared with not fulfilling any study criteria. In the second 12 months period, SENSCIS enriched patients had a further absolute FVC% decline as described for the total cohort. In contrast, patients fulfilling the focuSSced and SLS II inclusion criteria showed numerical improvement of lung function in the second period (Figure 1). There were no significant associations of enrichment criteria and ILD progression in the second period. Over the mean observation period of 2.3 years, patients not fulfilling any inclusion criteria showed the same FVC decline of –0.9 (12.1) as observed for the total cohort (–0.9% (12.6)). There were numerical differences in FVC changes in the enriched patient cohorts, varying from –2.8% FVC decline in patients fulfilling the focuSSced criteria to +3.4% FVC improvement with SLS II criteria. Conclusion Application of enrichment criteria from previous clinical trials showed enrichment for progression with variable success but led to selected patient populations reducing feasibility of recruitment. These findings are important for future clinical trial design and interpretation of the results of published trials. Acknowledgements We thank all EUSTAR collaborators. Disclosure of Interests Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp &amp; Dohme, Roche, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp &amp; Dohme, Roche, Grant/research support from: Boehringer Ingelheim, Cathrine Brunborg: None declared, Paolo Airò Speakers bureau: Bristol-Myers-Squibb, Boehringer Ingelheim, Consultant of: Bristol-Myers-Squibb, Grant/research support from: Bristol-Myers-Squibb, Roche, Jannsen, CSL Behring, Lidia P. Ananyeva Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, László Czirják Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Actelion (now GSK), MSD, Novartis, Pfizer, Roche, Lilly, Grant/research support from: Boehringer Ingelheim, Actelion (now GSK), MSD, Novartis, Pfizer, Serena Guiducci: None declared, Eric Hachulla Speakers bureau: GSK, Roche-Chugai, Johnson &amp; Johnson, Boehringer Ingelheim, Consultant of: CSL Behring, GSK, Roche-Chugai, Johnson &amp; Johnson, Boehringer Ingelheim, Grant/research support from: CSL Behring, Boehringer Ingelheim, GSK, Roche-Chugai, Sanofi Genzyme, Mengtao Li: None declared, Carina Mihai Speakers bureau: MEDtalks Switzerland, Mepha, Grant/research support from: Roche, Boehringer Ingelheim, Janssen, Gabriela Riemekasten Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Petros Sfikakis Consultant of: Boehringer Ingelheim, Gabriele Valentini Consultant of: Boehringer Ingelheim, Sanofi, Grant/research support from: BMS, Otylia Kowal-Bielecka Speakers bureau: Boehringer Ingelheim, Novartis, Pfizer, Gilead Sciences, Janssen-Cilag, MEDAC, MSD, Abbvie, Sandoz, Consultant of: Boehringer Ingelheim, Health Care system Navigator, CSL Behring, MSD, Novartis, Grant/research support from: CSL Behring, Boehringer Ingelheim, Abbvie, Roche, MEDAC, Yannick Allanore Speakers bureau: Boehringer, Abbvie, Consultant of: Boehringer, Bayer, Astra-Zeneca, Prometheus, Sanofi, Genentech/Roche, Boehringer, Grant/research support from: Alpine Immunosciences, OSE Immunotherapeutics, Medsenic, Oliver Distler Speakers bureau: Bayer, Boehringer Ingelheim, Janssen, Medscape, Consultant of: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, 4P Science, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Roivant, Sanofi and Topadur, Grant/research support from: Kymera, Mitsubishi Tanabe, Boehringer Ingelheim